氟伐他汀对心肌梗死后心衰大鼠内皮素-1表达的影响

Effect of Fluvastatin on the Expression of Myocardial ET-1 in Rats with Heart Failure after Acute Myocardial Infarction

目的探讨羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂氟伐他汀对急性心肌梗死后心衰大鼠内皮素-1(ET-1)表达变化的影响。方法雌性SD大鼠急性心肌梗死(AMI)术后6h随机分为心力衰竭对照组和氟伐他汀组,另设假手术组。直接灌胃给药8周后行高频多普勒超声、血流动力学、心脏重塑指标、左室非梗死区心肌ET-1 mRNA表达的测定。结果与假手术组比较,心力衰竭对照组左室舒张末期内径(LVEDD)、左室舒张末期容积(LVEDV)、E峰、E峰减速度、E/A、左室舒张末压(LVEDP)、左右心室心肌肥厚指数、非梗死区胶原容积分数(CVF)和ET-1 mRNA表达均显著增加(均P<0.01),左室短轴缩短率(FS)和射血分数(EF)均显著降低(均P<0.01)。与心力衰竭对照组比较,氟伐他汀组的LVEDD、LVEDV、E峰、E峰减速度、E/A、LVEDP和左、右心室心肌肥厚指数、CVF和ET-1 mRNA表达均显著降低(均P<0.01),FS和EF显著升高(均P<0.01)。结论ET-1参与了心肌梗死后的心肌纤维化和心衰进展,氟伐他汀抑制心肌梗死后心肌纤维化和心衰进展的作用机制至少部分与其下调ET-1表达有关。

Objective To investigate the effect of fluvastatin （FV） on the expression of endothelin-1（ET-1） mRNA of left ventricular （LV） myocardium in rats with heart failure after acute myocardial infarction （AMI）. Methods Six h after ligating left coronary artery, surviving AMI female SD rats were randomly assigned to~ heart failure control group; FV group; sham-operated group. After treatment for 8 weeks, cardiac function, hemodynamies, ventrieular remodeling parameters, ET-1 mRNA expression in the noninfarcted area （NIA） were assessed. Results As compared with sham-operated group, LV end diastolic dimension （LVEDD）, LV end-diastolic volume （LVEDV）, E-wave, E-wave deceleration, E/A ratio, LV end diastolic pressure （LVEDP）, LV relative weight （LVRW）, right ventricular relative weight （RVRW）, collagen volume fraction （CVF） and ET-1 mRNA expression in NIA were all significantly increased in heart failure control group （all P〈0. 01）, while fractional shortening （FS） and ejection fraction （EF） were significantly decreased （both P〈0.01）. In comparison with heart failure control group, LVEDD, LVEDV, E-wave, E-wave deceleration, E/A, LVEDP, LVRW, RVRW, CVF and ET-1 mRNA in NIA were all significantly decreased （all P〈0.01）, while FS and EF were significantly increased in FV group （both P〈0.01）. Conclusion ET-1 is involved in the ongoing cardiac fibrosis and progression of heart failure after AMI. The beneficial effects of FV on cardiac fibrosis and heart failure after AMI might be partly associated with the down-regulation of increased ET-1 levels.